Figure 4.

Lymphangiogenesis and its microfluidic models. A) Lymphangiogenesis in the developing embryo begins as ECs in the anterior cardinal vein begin expressing PROX-1, an event specifying their LEC fate. LECs migrate and form lymph sacs, or precursors to lymphatic vessels. As the lymph sacs mature, lymphangiogenic sprouts bud and form new lymphatic microvasculature. In the adult, lymphangiogenesis is uncommon except in pathological conditions, where sprouting follows similar EC events such as migration and proliferation in response to pro-lymphangiogenic factors such as VEGF-C. Reproduced with permission.^[82] 2010, Company of Biologists. B) Common chip designs in lymphangiogenesis MPSs. i) Micropost device situated across from fibrin-encapsulated NHLFs, similar to early angiogenesis-chips. Reproduced with permission.^[85] 2016, Elsevier. ii) Cylindrical lumen formed through sacrificial molding around solidified hydrogels, followed by endothelialization by LEC coating. Reproduced with permission.^[87] 2020, Royal Society of Chemistry. C) Examples of lymphangiogenesis-chips. i) LECs sprout in response to IF toward a parent lymphatic vessel and a combination of growth factors that alone induce less sprouting. Reproduced with permission.^[85] 2016, Elsevier. ii) Lymphatic vessels reported to exhibit higher lymphangiogenic sprouting in response to laminar flow (denoted LF) within the vessel. Scale bars = 100 μm. Reproduced with permission.^[94] 2017, American Society for Clinical Investigation.